microRNAs (miRs, miRNAs) are a family of 18-24 nucleotide long non-coding small RNAs, that suppress translation of target genes by binding to their mRNA, thereby regulating the expression of at least 30% of all human genes. There are currently about 850 known human microRNAs. Though highly conserved throughout evolution, a significant proportion of them is primate specific. microRNAs association with cancer has been demonstrated and several microRNAs have already been identified as oncogenes and tumor suppressors (He, H., et al., Proc Natl Acad Sci USA, 2005. 102(52): p. 19075-80).
One of the major characteristics of microRNAs is their marked tissue specificity. Many of them also exhibit temporal patterns of expression, suggesting that they play a critical role in specific tissues and in organ development, function and maintenance.
The differential diagnosis of hepatic lesions that include primary liver tumor and metastatic tumors is a frequent challenge in modern surgical pathology. Hepatic malignancies are often found in patients with advanced metastatic cancer. Identifying the origin of these tumors as well as differentiating liver metastases from primary hepatocellular carcinoma (HCC) is frequently required and poses a significant challenge that requires clinical-radiological correlation on top of careful pathological evaluation. Thorough examination assisted by a panel of immunostains is required for the identification of the origin of metastases. Extensive work-up using modern pathological tools (immunohistochemistry, electron microscopy and molecular diagnosis) and advanced imaging technology (computed tomography (CT), mammography and positron emission tomography (PET)) have resulted in some improvements in diagnosis. However, the primary site remains unknown in many patients, even on autopsy. The appropriate management of such patients is unclear and there is a high variability in clinical approaches, accompanied by poor prognosis in most cases.
The pathological characterization of brain malignancies remains a diagnostic challenge. Despite the advent of various high throughput genomic level technologies, which allow multiple DNA sequences, mRNAs or proteins to be evaluated simultaneously and systematically, these have had little impact on clinical procedures.
Differentiation between primary and metastatic tumors in the brain is often encountered in pathological practice, since metastatic tumors to the brain are quite frequent. The most common tumors to metastasize to the brain originate in the lung, breast and skin (melanomas); their respective contributions to all central nervous system (CNS) metastases are 30%, 20% and 10%. Although rare, choriocarcinoma disseminates to the brain with a particularly high frequency. In autopsy studies, 24% of cancer patients exhibited metastatic tumors in the CNS. Indeed, surgical pathologists are regularly presented with specimens from patients with a history of systemic neoplasia but with findings that suggest a primary intracranial tumor.
Therefore, there is a need for efficient and effective methods for the differentiation between primary and metastatic tumors.